Effects of kisspeptin on diabetic rat platelets

Abstract

Hyperglycemia, hyperlipidemia, and free radicals result in platelet activation and atherogenesis. Kisspeptin (KP) is able to regulate metabolism, hemostasis, and the development of atherosclerosis. We examined whether platelet aggregation of streptozotocin-induced diabetic rats depends on the inducer type and if KP-13 and RF-9 (a kisspeptin receptor modifier) can influence platelet function. We measured the speed and the maximum of aggregation, along with the area under the curve. Serum glucose and calcium levels and urine formation of diabetic animals increased, while the body mass and platelet count decreased. Collagen was the most effective inducer of platelet aggregation. The aggregability of nondiabetic platelets was elevated in the presence of 5 × 10 mol/L KP-13. This effect was less expressed in diabetic animals. The effectivity of RF-9 was stronger than that of KP-13 in nondiabetic platelets, however it was ineffective in diabetic animals. RF-9 pre-treatment did not change the effects of 5 × 10 mol/L KP-13 in either animal group. The in vivo activation of diabetic platelets, which may be due to elevated serum calcium, induces thrombocytopenia and may lead to reduced in vitro aggregability. We could not demonstrate the antagonistic effect of RF-9 against KP-13 in isolated platelets.

Effects of sub-chronic, in vivo administration of sigma-1 receptor ligands on platelet and aortic arachidonate cascade in streptozotocin-induced diabetic rats

“…None of the ligands significantly altered the STZ-induced increase in serum glucose concentration and decreased body weight gain ( Table 1 ), indicating they were unable to restore the STZ-induced metabolic changes. Consistent with our previous study [ 42 ], we found elevated serum cholesterol, ALT and urea levels in the STZ-induced diabetic animals, which may be explained by the hepatic and renal toxic effects of STZ [ 37 , 38 ]. The STZ-induced rise in serum ALT concentration was further boosted by the S1R ligands, although the growth was not significant for PRE-084 ( Fig 1 ).…”

“…These results suggest the metabolism and/or elimination of ligands in the liver or kidney [ 43 ]. The platelet count below the reference value [ 44 ], already observed in our previous study, can be explained by reduced thrombopoietin production due to the liver and kidney damage associated with STZ-induced diabetes [ 42 ]. However, in the present study, we only observed a trend towards a decrease in platelet counts in the STZ-treated animals compared to the vehicle-treated, healthy rat group, which was normalized by PRE-084 and NE-100.…”

Effects of sub-chronic,in vivoadministration of sigma-1 receptor ligands on platelet and aortic arachidonate cascade in streptozotocin-induced diabetic rats

“…The platelet count below the reference value, 30 already observed in our previous studies, could be explained by reduced thrombopoietin production due to the liver and kidney damage associated with STZ-induced diabetes. 39 Sub-chronic treatment with S1R ligands had, no effect on platelet formation, although this is not relevant in the present study as eicosanoid synthesis was monitored at a standard platelet count (2.5×10 8 platelets/μL) (Table 1) .…”

“…Platelets primarily produce the vasoconstrictor thromboxane, which induces platelet aggregation, and the endothelium primarily produces the vasodilator prostacyclin, which inhibits platelet aggregation, but under physiological conditions these products are in equilibrium to ensure normal local circulation. 31,39,44…”

“…Platelets primarily produce the vasoconstrictor thromboxane, which induces platelet aggregation, and the endothelium primarily produces the vasodilator prostacyclin, which inhibits platelet aggregation, but under physiological conditions these products are in equilibrium to ensure normal local circulation. 31,39,44 Taken together, ligands have opposite effects on platelet and aortic AA metabolism in the diabetic rat, which may promote the pursuit of physiological equilibrium, even under pathological conditions.…”